TW201902497A - Method for producing nasal spray composition and nasal spray composition - Google Patents

Abstract

The purpose of the present invention is to provide a production method of a nasal drop composition suitable for the treatment or prevention of disease or symptoms in the nasal cavity, and a nasal drop composition obtained by said production method. This production method of a nasal drop composition is characterized by involving a mixing step for mixing earthworm castings and water, and a recovery step for obtaining a liquid by recovering vaporized water generated from the mixture obtained in the mixing step; this nasal drop composition is obtained by said production method. In the mixing step, it is favorable to further mix organic matter in addition to the earthworm castings and the water.

Description

Method for manufacturing nose point composition and nose point composition

The present invention relates to a method for manufacturing a nasal agent composition suitable for treating or preventing a disease or symptom in the nasal cavity, and a nasal agent composition obtained by the manufacturing method.

In the past, a nasal agent composition has been used for the treatment or prevention of hay fever or empyema. Various studies have been conducted on such a nasal preparation composition (for example, Patent Documents 1 and 2), but generally, a nasal preparation composition that is different from the past is being sought from the point that it is difficult to show effects depending on the subject. . [Prior Art Literature] [Patent Literature]

Patent Document 1: Japanese Patent No. 4591810 Patent Document 2: Japanese Patent No. 4790096

[Problems to be Solved by the Invention]

Therefore, an object of the present invention is to provide a method for producing a point-injection composition suitable for treating or preventing a disease or symptom in the nasal cavity, and a point-injection composition obtained by the method. [Means for solving problems]

As a result of an intensive review by the present inventors in order to solve the above-mentioned problems, it was found that the liquid obtained by recovering the vaporized water generated when the dung of earthworms is mixed with water is suitable for the treatment or prevention of diseases or symptoms in the nasal cavity Then completed the present invention.

That is, the method for producing a nasal agent composition of the present invention is characterized by including a mixing step of mixing earthworm dung and water, and recovering the vaporized water generated from the mixture obtained in the aforementioned mixing step to obtain a liquid. Of recovery steps.

The method for producing the nasal agent composition of the present invention is preferably a step of mixing the organic matter with the dung of the earthworm and the water in the mixing step.

In the method for producing a nasal composition according to the present invention, the organic substance is preferably wood.

The method for producing a nasal agent composition of the present invention preferably further comprises a dilution step of diluting the liquid obtained by recovering the vaporized water in the aforementioned recovery step with water.

The nasal point composition of the present invention is characterized in that it is obtained by the aforementioned method for producing a nasal point composition.

The nasal agent composition of the present invention is preferably used in a mist form.

The nasal agent composition of the present invention is preferably used for treating or preventing a disease or symptom in the nasal cavity.

In the nasal preparation composition of the present invention, the aforementioned disease or symptom in the nasal cavity is preferably hay fever or empyema.

The method for treating hay fever or empyema according to the present invention is characterized in that the aforementioned nasal agent composition is administered to a patient.

The nasal agent composition of the present invention is preferably used for treating hay fever or empyema. [Inventive effect]

According to the present invention, it is possible to provide a method for manufacturing a nasal agent composition suitable for treating or preventing a disease or symptom in the nasal cavity, and a nasal agent composition obtained by the manufacturing method.

The method for producing a nasal preparation composition according to the present invention is characterized by including a mixing step of mixing earthworm dung and water, and a recovery step of recovering vaporized water generated from the mixture obtained in the aforementioned mixing step. Preferably, in the mixing step, an organic substance is further mixed with the dung of the earthworm and the water together. Although the detailed mechanism is unknown, it is generally believed that microorganisms such as bacteria contained in earthworm's dung will decompose and ferment organic matter contained in earthworm's dung or separately mixed organic matter, and recover the liquid obtained by vaporizing water. It is effective in treating or preventing diseases or symptoms in the nasal cavity.

Hereinafter, the manufacturing method of the nasal point composition and the nasal point composition of this invention are demonstrated in detail.

[Manufacturing method of nasal preparation composition] (Mixing step) The mixing step is a step of mixing dung of earthworms with water.

The dung of the earthworm is not particularly limited, and for example, red earthworm (Lumbricus rubellus), LT earthworm (Lumbricus terrestris), Eisenia foetida, Allolobophora caliginosa, Dendrobaena octaedra, Allolobophora japonica Michaelsen, Drawida hattamimizu Hatai, Phertima divergens Michaelsen, Phertima communissima, Phertima agrestis, Pheretima sieboldi Horst The dung soil of Phyletima hilgendorfi, Pontodrilus matsushimensis Iizuka, Tubifex hattai Nomura, Goto silk earthworm (Limnodrilus gotoi Hatai = L. Socialis Stephenson) and the like.

The water to be mixed with the dung of the earthworm is not particularly limited, and tap water or distilled water can be used. In addition, water can also be purified by using a filter material, a reverse osmosis membrane, and the like. From the viewpoint of removing microorganisms such as bacteria, it is preferable to use a microporous filter material or a reverse osmosis membrane, etc., and it is preferable to use, for example, a SPG (white sand porous glass) penetration membrane.

The mixing ratio of earthworm's dung and water is per kg of earthworm's dung, the water is preferably 0.05-20L, more preferably 0.1-10L, even more preferably 0.2-5L, and particularly preferably 0.5-2L.

In the mixing step, it is preferable to further mix the organic matter with the dung and water of the earthworm. When organic substances are mixed, a nasal preparation composition which is more effective in the treatment or prevention of diseases or symptoms in the nasal cavity can be obtained, and the pH of the nasal preparation composition can also be adjusted. The organic substance is not particularly limited as long as it can be mixed with the fecal soil of earthworms and decomposed. For example, organic substances derived from organisms such as animals, plants, fungi, and protozoa can be used. Examples of the plant-derived organic matter include wood such as wood chips, sawdust, and chaff, and fungal beds used in the cultivation of mushrooms. If the mixed wood is used as an organic substance, the odorless liquid can be easily recovered in the recovery step. As the wood, a wood piece is preferred. In addition, the wood species is not particularly limited, and may be conifers such as yew, cypress, Japanese cypress, Japanese cedar, Japanese cedar, golden pine, pine, cedar, spruce, fir, iron spruce, and sequoia. Broad-leaved trees such as cherry, oak, beech, beech, birch, vertebra, maple, alder, alder, Japanese hornbeam, bamboo. Among the woods, pine wood can be suitably used. More preferably, wood of the cypress family can be used, and wood of the subfamily cypress subfamily can be suitably used, and wood of the genus Japanese cedar is particularly suitably used.

The mixing ratio of earthworm soil and organic matter is 1kg of earthworm soil, preferably organic matter is 0.05-20kg, more preferably 0.1-10kg, even more preferably 0.2-5kg, and particularly preferably 0.5-2kg.

The mixing method in the mixing step is not particularly limited, and it is preferable to sufficiently mix the mixture by performing stirring or the like. The order of mixing is not particularly limited. For example, the container may be filled with earthworm dung and organic matter, and water may be added. Alternatively, the container may be filled with organic matter and water, and then earthworm dung may be added.

It is not necessary to mix the total amount of each component at one time, and water, earthworm soil and / or organic matter can be added and divided into multiple times for mixing. By continuing the addition, it is preferable to continuously replenish vaporized water while replenishing the water or water that is reduced by decomposition or the dung or organic matter of earthworms that are reduced by decomposition.

In addition, if the time elapses from the initial mixing, the fermentation is more stable. Therefore, if the vaporized water is recovered after the passage of time in about one day, for example, the effect of treating or preventing diseases or symptoms in the nasal cavity can be more excellent. Liquid. From this point of view, it is also preferable to perform continuous addition and continuously recover the vaporized water.

In the mixture, heat is generated due to the fermentation of earthworm dung or organic matter added separately. It is preferred that the mixture be heated while heating according to the air temperature. When the heating is performed, the heating may be performed to, for example, 30 to 50 ° C.

(Recovery step) (1) The recovery step is a step of recovering the vaporized water generated from the mixture obtained in the mixing step to obtain a liquid (hereinafter, also referred to as "organic matter decomposition water"). It is also possible to perform the mixing step and the recycling step simultaneously.

In the recovery step, it is only necessary to recover the vaporized water generated in the temperature range raised by the fermentation heat (reaction heat) generated by the fermentation of the mixture, and it is not necessary to heat to the boiling point. It is preferable to perform mixing while heating according to the air temperature. When heating, the heating may be performed to, for example, 30 to 50 ° C.

The method for recycling is not particularly limited as long as the vaporized water can be recovered, and for example, the vaporized water can be recovered using a dehumidifier. As the dehumidifier, for example, a dehumidifier of a cooling method or a compression method can be used. In addition, it is preferable to recover the vaporized water without boiling the mixture.

The method for making the recovered vaporized water into a liquid is not particularly limited, and for example, as long as it is recovered by using a dehumidifier, organic decomposed water can be obtained. The dehumidifier is not particularly limited as long as it can recover vaporized water as a liquid, and a dehumidifier of a cooling method or a compression method can be used, for example.

The pH of the liquid obtained by recovering the vaporized water is preferably 5 to 9, more preferably 6 to 8, and even more preferably 6.5 to 7.5.

(Dilution step) Although the organic matter decomposed water obtained by recovering the vaporized water in the recovery step may be used as the nose drop composition as it is, it is preferably diluted and used. As the solvent for dilution, as long as water is used, tap water or distilled water can be used. In addition, the water used for dilution can also be purified by using filter materials, reverse osmosis membranes, etc. From the viewpoint of removing microorganisms such as bacteria, it is preferable to use a microporous filter material or a reverse osmosis membrane, etc., and it is preferable to use, for example, a SPG (white sand porous glass) penetration membrane.

In the case of dilution, the dilution may be, for example, 1.5 to 10 times, preferably 4 to 6 times, and more preferably 4.5 to 5.5 times.

[Nasal preparation composition] 特征 The nasal preparation composition of the present invention is characterized by being obtained by the method for producing a nasal preparation of the present invention. The nasal agent composition of the present invention is not particularly limited as long as it is obtained by the manufacturing method of the nasal agent composition of the present invention and is effective for treating or preventing a disease or symptom in the nasal cavity, and is preferably liquid. In addition, the liquid nasal point composition can be sprayed or evaporated into a mist and used. Further, it may be mixed with, for example, an excipient and processed into a solid form such as a gel, a powder, or a granule.

The nasal agent composition of the present invention may further include a pharmaceutically acceptable carrier. As a pharmaceutically acceptable carrier, an excipient, a binder, a disintegrant, a fluidizer, a lubricant, a coating agent, a suspending agent, a coloring agent, a sweetener, or a surfactant can be used. A known method is used to form a general pharmaceutical preparation. In addition, other therapeutic / prophylactic ingredients or pharmaceutically acceptable additives may be included.

The blending amount of the liquid recovered in the aforementioned recovery step in the nasal preparation composition of the present invention may be an effective amount according to the purpose. The appropriate blending amount depends on various factors such as the purpose, shape, and manufacturing conditions. For example, in the case of a liquid nosedrop composition, the blending amount of the liquid recovered in the foregoing recovery step is only 5 The vol% or more may be sufficient, preferably 5 to 50 vol%, more preferably 10 to 40 vol%, and even more preferably 20 to 30 vol%.

In addition, the amount of the nasal agent composition of the present invention may be an effective amount according to the purpose. The appropriate amount depends on various factors such as the purpose, shape, manufacturing conditions, and symptoms. For example, when the liquid nose preparation composition is sprayed into the nasal cavity, it only needs to be used every day. Spread 6-10 times.

The nasal agent composition of the present invention is preferably used for treating or preventing a disease or symptom in the nasal cavity. The diseases or symptoms in the nasal cavity are not particularly limited, and examples thereof include hay fever and empyema.

In the nasal point composition of the present invention, other effective ingredients, or well-known conventional additives used in the nasal point composition, such as a coloring agent, a fragrance, and an antioxidant, may be added within a range that does not impair the effects of the present invention. , UV absorber, chelating agent, surfactant, viscosity adjuster, pH adjuster, thickener, defoamer, preservative, bactericidal / antibacterial agent, dispersant, organic solvent, etc.

In addition, in the nasal preparation composition of the present invention, a dry powder, a ground product and / or an extract of earthworm may also be blended. By mixing the dry powder, grind and / or extract of earthworm, a liquid with better effect of treating or preventing diseases or symptoms in the nasal cavity can be obtained. Among these, an earthworm extract is more preferable from the viewpoint of obtaining more excellent effects. As the extract of the earthworm, for example, an extract obtained by extracting the dried powder of the earthworm with water, ethanol, or an aqueous ethanol solution can be used.

The earthworm used in the raw material is not particularly limited, and for example, red earthworm (Lumbricus rubellus), LT earthworm (Lumbricus terrestris), Eisenia foetida, Allolobophora caliginosa, and Dendrobaena octaedra), Allolobophora japonica Michaelsen, Drawida hattamimizu Hatai, Pheretima divergens Michaelsen, Pheretima communissima, Pheretima agrestis, Pheretima bolus Horst), Pheretima hilgendorfi, Lakeside earthworm (Pontodrilus matsushimensis Iizuka), Silkworm (Tubifex hattai Nomura), Goto Silkworm (Limnodrilus gotoi Hatai = L. Socialis Stephenson) and the like.

As used herein, the term "dried powder of earthworms" means powder obtained by drying ground or ground extracts of untreated or pretreated earthworms. In addition, the ground earthworm is a liquid or pasty substance obtained by grinding an untreated or pretreated earthworm. The so-called earthworm extract means an extract obtained by dissolving untreated or pretreated earthworm or its ground material in water or an organic solvent to remove or separate insoluble portions. The pretreatment is not particularly limited, and examples thereof include removal treatment of dirt and the like described later. In addition, the dried powder, ground material, and extract of the earthworm may be subjected to post-treatment. Examples of the post-treatment include granulation, filtration, purification, concentration, dilution, and pH adjustment.

The grinding method for obtaining the ground material of the earthworm is not particularly limited, and it can be ground using, for example, a homogenizer, a blender, a homomixer, a crusher, a pressurized cell destruction device, or the like.

The extraction method for obtaining the extract of the earthworm is not particularly limited. For example, the dried powder or ground material of the earthworm can be dissolved in the extraction solvent, and the insoluble portion can be removed or separated for extraction. Examples of the extraction solvent include water, an aqueous solution, and organic solvents such as ethanol, acetone, and ethyl acetate. These solvents may be used alone or in combination of two or more. Among these, water, ethanol, or an ethanol aqueous solution is preferred.

The drying method for obtaining the dried matter of the earthworm is not particularly limited, and it can be dried by drying methods such as freeze drying, heat drying, and spray drying. Among these, freeze drying is preferred for reasons described later.

It is preferable to remove the digestive matter remaining in the digestive tube of the earthworm, the dirt adhering to the body skin, and the like. The removal method is not particularly limited, and it can be removed by a known method. For example, a method in which earthworms are immersed in an aqueous solution of an alkali metal salt such as sodium salt or potassium salt to excrete the loess in the digestive tract can be used (Japanese Patent Laid-Open No. 1-48718, Japanese Patent Laid-Open No. 1- 47719, Japanese Patent Laid-Open No. 1-47720, and Japanese Patent Laid-Open No. 1-268639), and the earthworms are kept in an acid aqueous solution maintained at 6 to 26 ° C for 0.1 to 5 hours to remove A method of digestive soil in a digestive tube (the method described in Japanese Patent Laid-Open No. 3-72427) and the like.

As a removal method, it is preferable to contact the chlorides and / or hydroxycarboxylic acids of the following metals with earthworms.

The chloride of the metal is a chloride of at least one metal selected from the group consisting of potassium, sodium, magnesium, and calcium. That is, it is at least one selected from the group consisting of potassium chloride, sodium chloride, magnesium chloride, and calcium chloride. In addition, it may be a mixture of these, or a mixture of these and other harmless ingredients that can be added to food. Examples of such a mixture include table salt, rock salt, and sun salt. The chloride of the above metal can be used by dusting a powdered substance to live earthworms, whereby contact between the earthworm and the chloride of the metal occurs.

After the chloride of the metal is brought into contact with the live earthworm, it is preferable to contact the hydroxycarboxylic acid with the live earthworm as described below. In addition, the contact of the hydroxycarboxylic acid and the earthworm may be performed as described below without contacting the metal chloride.

The contact with the said hydroxycarboxylic acid can also be performed by dusting a powdery hydroxycarboxylic acid to a living earthworm. Alternatively, it may be immersed in a hydroxycarboxylic acid aqueous solution having a pH of 2 to 5. In the case where contact with a hydroxycarboxylic acid is performed after contact with a chloride of a metal, contact with a hydroxycarboxylic acid is preferably performed immediately after contact with a chloride of the metal. In addition, the earthworm is preferably washed with water before the live earthworm is brought into contact with the hydroxycarboxylic acid. If the metal chloride is removed by washing with water and then the earthworm is contacted with the hydroxycarboxylic acid, a dried earthworm powder having a higher enzyme activity can be obtained. In the case of washing with water before contacting with hydroxycarboxylic acid, the washing with water is preferably performed within 30 minutes, more preferably within 20 minutes after the contact with the metal chloride is started. The water washing method is not particularly limited, and a known method can be adopted.

If the living earthworm is kept in contact with the hydroxycarboxylic acid powder for a long time, it will die, lose its life function, and will not excrete the digestive material in the digestive tract. Therefore, it is preferably as fast as possible, preferably 30. Within seconds, more preferably within 20 seconds, the hydroxycarboxylic acid is diluted with water, and the pH is adjusted to a range of 2 to 5.

Because hydroxycarboxylic acids will form a living environment that is uncomfortable for earthworms, living earthworms will try to improve the living environment by self-preserving instincts to release body fluids and excreta. In addition, since hydroxycarboxylic acid has a bactericidal effect, it is expected to have the effect of sterilizing the germs attached to earthworms while promoting the excretion of digestive matter and the like remaining in the digester as described above.

The crystalline hydroxycarboxylic acid used in the above method can be used as long as it shows crystals under the conditions of use, that is, regardless of the number of hydroxyl groups or carboxyl groups. That is, it may be any of a monohydroxy monocarboxylic acid, a monohydroxy polycarboxylic acid, a polyhydroxy monocarboxylic acid, and a polyhydroxy polycarboxylic acid.

Examples of the hydroxycarboxylic acid include glycolic acid, lactic acid, acetic acid, β-hydroxypropionic acid, α-hydroxyn-butyric acid, β-hydroxyn-butyric acid, α-hydroxyn-glyoxylic acid, β-hydroxyn-glycyrrhizic acid, malic acid, α- Methyl malic acid, α-hydroxyglutaric acid, β-hydroxyglutaric acid, citric acid, malonic acid, and succinic acid. Among these, lactic acid, acetic acid, malic acid, citric acid, malonic acid, and succinic acid are preferable because they can be used for food and are easily available. A hydroxycarboxylic acid may be used individually by 1 type, and may mix and use 2 or more types.

65% of the tissues of live earthworms are water. Although there is a certain amount of time for the life-saving function of the live earthworm, the enzyme will work if the live earthworm dies, so the control of the time of being placed in an uncomfortable living environment must be carefully implemented. This time is subject to conditions and is usually in the range of 3 to 180 minutes.

It is preferable that the living body of the earthworm treated with hydroxycarboxylic acid is washed with water and then ground to make a liquid or paste-like ground material. Washing is preferably performed with pure water. The washing method is not particularly limited, and a known water washing method can be used. In addition, the total time of the processing steps before grinding, that is, the time from when the metal chloride is sprinkled to live earthworms until the washing with water using hydroxycarboxylic acid is completed, is preferably less than 240 minutes in total.

The above-mentioned grinding method is not particularly limited, and for example, a homogenizer, a blender, a homomixer, a crusher, and a pressurized cell destruction device can be used, and it is usually carried out at 1 to 25 ° C. From the viewpoint of suppressing the decomposition of the earthworm constituents, it is preferably performed at a low temperature, and a temperature of 2 to 15 ° C is preferred.

The ground material obtained by grinding the earthworm is housed in, for example, a stainless steel tray and delivered to freeze-drying. At this time, since the enzymes contained in the earthworm's living body will not act on living cells but will instantly act on dead cells, there is a concern of generating spoilage gases. In order to prevent this, it is best to quench / freeze instantly After -18 ° C to -35 ° C to inhibit the effect of enzymes, freeze-drying is performed.

In this way, in order to powderize without harming the original pharmacological action of the earthworm, it is preferable to freeze it quickly, but on the other hand, if it is frozen in a short period of time, there will be In the case where impurities commonly present in the protein of the main component form a spot-like unfrozen portion and cannot be separated, excessively rapid freezing is not preferable. Therefore, freezing is preferably performed at a low temperature of -18 ° C to -35 ° C, which takes 20 to 240 hours, more preferably 50 to 170 hours.

In freeze-drying, it is important to select conditions that can remove impurities and moisture without leaving them. For this reason, it is preferable to perform the temperature control stepwise within a range of 10 to 60 hours while gradually increasing the temperature at a temperature of 50 Pa or lower and a temperature of -60 ° C to + 90 ° C.

As a method of freeze-drying, for example, the ground material can be frozen at a temperature of -18 ° C to -35 ° C for 20 to 240 hours as described above, and then divided into several parts at a temperature of -60 ° C to + 90 ° C. The temperature was raised in stages, and the pressure was divided into several stages at a pressure of 25 to 40 Pa. The pressure was reduced and freeze-dried for 10 to 60 hours to obtain a dry yellow earthworm powder in a sterile state.

Furthermore, it is preferable to include a step of dissolving the ground lyophilized product in water or an aqueous ethanol solution to remove or separate the insoluble portion. The steps of removing or separating the insoluble portion are the same as those described above, and precipitation, centrifugation, filtration, and the like which are left to stand can be used. The step of dissolving in water or an aqueous ethanol solution is preferably performed while stirring or shaking. The time required to dissolve in water is preferably 1 to 120 minutes, and more preferably 5 to 80 minutes. The ethanol concentration of the ethanol aqueous solution is not particularly limited, but is preferably 10 to 70% (v / v), and more preferably 30 to 60%.

As the earthworm extract, the supernatant obtained by dissolving it in water or an aqueous ethanol solution as described above can be used as it is in the form of an aqueous solution, or the water can be removed and used as a concentrated solution. It is dried and used as a powder. It is also possible to dissolve and use the supernatant obtained by drying and powdering the supernatant. In addition, the powder obtained by freeze-drying the earthworm paste can be used as it is without being dissolved in water or an aqueous ethanol solution.

In addition, as a removal method, it is preferable to move the live earthworm to a bread box, for example, before the live earthworm is placed in an uncomfortable environment, that is, before the live earthworm is exposed to a metal chloride or hydroxycarboxylic acid. In a flat box, leave it in a bright place for 10-50 hours to remove the dirt attached to the body skin. The storage time in a bright place is more preferably 12 to 24 hours. The yield at this time is preferably an amount in which earthworms accumulate to a thickness of 30 to 60 mm, and more preferably 40 to 50 mm. In this flat box, foreign matter such as sand and mud does not exist. In addition, earthworms are nocturnal, living activities in the dark will become lively, and there will be doubts about physical exertion. Therefore, it is better to use electric lighting at night. Cultivation methods, etc. remain bright. With this treatment, the live earthworm will exert its self-defense instinct, excrete the digestive residues remaining in the digestive tract, and use this excrement to cover the whole body and prevent the evaporation of water, in an attempt to maintain the living environment. Therefore, as long as it is stripped by appropriate means The covered dirt, that is, fecal matter, can finally remove the digestive matter in the digestive tract and the dirt attached to the body skin.

The removal of the dirt adhering to the body skin of an earthworm can be performed by coating a living earthworm with a nonwoven fabric, and adsorb | sucking a dirt to this nonwoven fabric, for example. It is expected to further excrete and remove the toxic substances in the earthworm body by a combination of the removal of the dirt placed on the bright place and the adhesion to the body skin, and the contact with the metal chloride and / or hydroxycarboxylic acid.

As a method of obtaining a dry powder of earthworm, from the viewpoint of storage stability of the dry powder, the following method is preferred. (A-1) A method for producing a dry powder of earthworms, comprising the steps of: (i) bringing a live earthworm into contact with a chloride of at least one metal selected from the group consisting of potassium, sodium, magnesium, and calcium; and The powdery hydroxycarboxylic acid is brought into contact with live earthworms, diluted with water and adjusted to a pH of 2-5, and maintained for 3 to 180 minutes, then the live earthworms are washed with water, ground, and the obtained ground material is freeze-dried. . (A-2) A method for producing a dry powder of earthworms, comprising the steps of: contacting a live earthworm with a chloride of at least one metal selected from the group consisting of potassium, sodium, magnesium, and calcium, and then, The live earthworm is immersed in an aqueous solution of hydroxycarboxylic acid adjusted to a pH of 2 to 5 and maintained for 3 to 180 minutes, and then the live earthworm is washed with water and ground, and the obtained ground material is freeze-dried. (A-3) A method for producing a dry powder of earthworms, which comprises the following steps: (1) In the aforementioned (A-1) or (A-2), dissolving a substance obtained by freeze-drying the ground material in water After removing or separating the insoluble portion in the aqueous ethanol solution, the step of freeze-drying is further performed.

In addition, after the ground material obtained by pulverizing the live earthworm is freeze-dried, the obtained dried material may be heat-treated from the viewpoint of sterilization of the dried material. The temperature of the heat treatment is preferably 110 ° C or higher and less than 130 ° C. If the heating temperature is lower than 110 ° C, the sterilization of the dried material may be insufficient. If the heating temperature is 130 ° C or higher, the enzymes contained in the dried earthworms will be inactivated and the activity will be reduced, which is not good. It is more preferably 115 to 125 ° C. The heating method is not particularly limited, and examples thereof include a method of applying hot air, a method of using a heating jacket, a method of placing on a tray and heating with a heater, and a method of using a constant temperature thermostat. The heating time is preferably 30 seconds to 130 minutes, more preferably 30 minutes to 90 minutes, and even more preferably 60 minutes to 90 minutes. If the heating time is too short, the sterilization may be insufficient, and if it is too long, the activity of the enzyme will be lost, so it is not good. In addition, if the above-mentioned heat treatment is performed on the enzyme in the liquid, the enzyme activity will be lost, so the heat treatment is preferably performed on the dried powder of the earthworm.

As a method of obtaining the ground material of earthworm, the following method is preferable. (B-1) A method for producing a ground material of earthworms, comprising the steps of: contacting a live earthworm with a chloride of at least one metal selected from the group consisting of potassium, sodium, magnesium, and calcium, and then, The powdery hydroxycarboxylic acid is brought into contact with live earthworms, diluted with water and adjusted to a pH of 2 to 5, and maintained for 3 to 180 minutes, and then the live earthworms are washed with water and ground. (B-2) A method for producing a milled earthworm, comprising the steps of: (i) bringing a live earthworm into contact with a chloride of a metal selected from the group consisting of potassium, sodium, magnesium, and calcium; It is a step of immersing in a hydroxycarboxylic acid aqueous solution adjusted to a pH of 2 to 5 and holding it for 3 to 180 minutes, and then washing and grinding the live earthworm.

As a method for obtaining an extract of earthworm, the following method is preferred. (C-1) A method for producing an extract of earthworms, comprising the steps of: (i) contacting a live earthworm with a chloride of at least one metal selected from the group consisting of potassium, sodium, magnesium, and calcium; and The powdery hydroxycarboxylic acid is brought into contact with live earthworms, diluted with water and adjusted to a pH of 2-5, and maintained for 3 to 180 minutes. The live earthworms are washed with water, ground, and the obtained ground material is freeze-dried. The obtained product is dissolved in water or an aqueous ethanol solution, and the step of removing or separating the insoluble portion is performed. (C-2) A method for producing an extract of earthworms, which comprises the following steps: contacting a live earthworm with a chloride of a metal selected from the group consisting of potassium, sodium, magnesium, and calcium, and then immersing the live earthworm The hydroxycarboxylic acid aqueous solution adjusted to a pH of 2 to 5 is maintained for 3 to 180 minutes, and then the live earthworms are washed with water and ground to dissolve the obtained ground material by freeze-drying in water or an ethanol aqueous solution. Step of removing or separating the insoluble portion.

The blending amount of the earthworm's dry powder, ground material and / or extract is not particularly limited. In the case of a liquid oral composition, the dry mass of the extract obtained by extraction with water is converted. The nasal preparation composition is, for example, 0.1 to 100 mg per 100 L, suitably 0.2 to 50 mg, and more preferably 1 to 20 mg. [Example]

Hereinafter, the present invention will be described in more detail through examples. The invention is not limited in any way by the following examples. It should be noted that the "%" hereinafter will be referred to as the quality standard unless specifically determined.

(Water decomposed by organic matter) 40Add 40L of water to the reaction tank filled with 40kg of red earthworm dung and 15kg of wood (Japanese cedar) (5kg of wood chips and 10kg of sawdust or chaff mixture), while stirring, while The vaporized water was recovered in a dehumidifier (NAKATOMI Corporation, DM-30) installed in the reaction tank in about 1 day, and a liquid of 15 to 20 L was obtained. Add 10-20L of water and 10kg of wood (Japanese cedar) into the reaction tank (5kg of wood chips and 5kg of sawdust or husk mixture), and similarly collect the vaporized water with a dehumidifier for about 1 day to recover. 15 to 20 L of liquid was obtained. About 40 L of liquid (pH 8.71) obtained by mixing the obtained liquids was obtained as organic matter decomposed water. In the production of the organic-decomposed water, as the water, water obtained by subjecting tap water to a water purification treatment with an SPG (white sand porous glass) penetration film (manufactured by SPG Techno) and activated carbon is used.

(Earthworm extract) After being left in a bright place for 24 hours, 30 kg of live red earthworms that had adhered to the body skin's dirt were peeled and laid on a flat plate to a thickness of about 5 cm, and 250 g of sodium chloride was evenly sprinkled thereon. After 20 minutes, the earthworms were washed with water. Then, similarly, 250 g of citric acid was sprinkled, and 30 liters of pure water was added for 15 seconds to dilute. At this time, the pH immediately after the addition of water was 2.25, and the pH when completely diluted was 2.74. Once the citric acid powder is sprinkled, the earthworms release yellow body fluid in one breath. After dilution with water, this state was maintained for 20 minutes. Next, the live earthworm was taken out from the dirty citric acid aqueous solution, washed with water, and then ground using a homogenizer at 10 ° C to prepare an earthworm paste. Next, this earthworm paste was degassed by suction to remove the gas contained therein, and then moved to a stainless steel tray, and then rapidly cooled to -35 ° C, and then frozen at this temperature for 50 hours. The frozen earthworm paste was kept at a pressure of 0 Pa at -35 ° C for 2 hours, and then heated to a temperature of 25 ° C, dried at 40 Pa for 10 hours, and then dried at 40 ° C and 35 Pa for 14 hours, and then at 65 ° C and 35 Pa. After drying for 12 hours, the temperature was finally set to 80 ° C., and the pressure was kept at 25 Pa for 6 hours to perform vacuum freeze-drying. By this treatment, a pale yellow dried earthworm powder having a water content of 8% by mass was obtained.

From the dried earthworm powder obtained above, 25 g was taken, 500 mL of distilled water was added, and the mixture was extracted with stirring at room temperature for 1 hour. The obtained extract was centrifuged (10,000 × g, 4 ° C, 15 minutes), and the supernatant was collected to obtain an earthworm extract. The obtained extract was micronized in a freeze vacuum dryer, 30 mg was taken, and 500 mL of distilled water was used to obtain a diluted stock solution.

(Nose point composition) The organic matter decomposed water obtained above was diluted 5 times with water. Here, as the water used for the dilution, tap water was obtained by purifying water with a SPG (white sand porous glass) penetration membrane (manufactured by SPG Techno) and activated carbon. The diluted organic decomposed water and the diluted stock solution of the earthworm extract obtained above are mixed at a ratio of 1000: 1, and passed through a 0.2 μm filter to obtain a nasal preparation composition.

Example 1 <Pollenosis 1> Observe that the nasal preparations obtained above have been sprayed 2 to 5 times with a commercially available nasal cleansing sprayer daily, once a day, 6 to 10 times, and once Symptoms of hay fever scattered in the nasal cavity of the following subjects.验 Subject: Female, 22 years old: 2 years of medical history 3rd day, nasal water and tears decreased 日 7th day, nasal water and tears stopped 15 days later, hay fever pain was relieved 减轻 30 days later, healed

Example 2 <Pollenosis 2> Observe that the nasal preparations obtained above have been sprayed 2 to 5 times with a commercially available nasal cleansing sprayer daily, once a day, and once every day. Symptoms of hay fever scattered in the nasal cavity of the following subjects.验 Subject: Male, 52 years old: 15 years of medical history After 7 days, nasal irritation and itching in the eyes decreased After 14 days, nasal water and itching disappeared After 25 days, symptoms improved After 30 days, symptoms disappeared

Example 3 <Pyresis 1> Observe that the nasal preparation obtained above was spread 6 to 10 times a day, once a day with a commercially available nasal cleansing sprayer 2 to 5 times. Symptoms of empyema in subjects described below sprayed in the nasal cavity.验 Subject: Male, 18 years old: 2 months of medical history, with yellow nose 水 After 7 days, the amount and color of nasal water will decrease 鼻 After 10 days, the nasal water will stop After 25 days, the nasal opening will be cured

Example 4 <Empty Symptom 2> Observe that the nasal preparations obtained above were spread 6 to 10 times a day, once a day with a commercially available nasal cleansing sprayer 2 to 5 times. Symptoms of empyema in subjects described below sprayed in the nasal cavity.验 Subject: Female, 15 years old: 1 month of medical history After 3 days, the nasal fluid decreased After 7 days, the nasal fluid stopped After 15 days, the nasal opening was cured

As shown in Examples 1 to 4, it was found that a nasal agent composition suitable for treating or preventing a disease or a symptom in the nasal cavity can be produced by recovering vaporized water produced by a mixture of earthworm scat and water.

Claims (10)

A method for manufacturing a nasal preparation composition, comprising a mixing step of mixing earthworm dung and water, and a step of recovering liquid obtained by vaporizing water generated from the mixture obtained in the foregoing mixing step to obtain a liquid. . For example, in the method for manufacturing a nasal preparation composition according to item 1 of the scope of patent application, in the aforementioned mixing step, an organic substance is further mixed with the dung of the earthworm and the aforementioned water together. For example, the method for manufacturing a nasal composition according to item 2 of the patent application, wherein the organic substance is wood. For example, the method for manufacturing a nasal agent composition according to item 1 of the patent application scope further includes a dilution step of diluting the liquid obtained by recovering the vaporized water in the aforementioned recovery step with water. A nasal point composition is characterized in that it is obtained by a method for manufacturing a nasal point composition according to item 1 of the scope of patent application. For example, the nasal composition of point 5 in the scope of patent application is used in the form of a mist. For example, the nasal composition of point 5 or 6 of the scope of patent application is used to treat or prevent diseases or symptoms in the nasal cavity. For example, the nasal composition according to item 7 of the application, wherein the disease or symptom in the nasal cavity is hay fever or empyema. A method for treating hay fever or empyema is performed by administering a nasal agent composition to the patient in the seventh item of the patent application. For example, the nasal composition of point 7 in the scope of patent application is used for the treatment of hay fever or empyema.